Women whose mothers experienced early menopause are themselves likely to have an accelerated decline in fertility, Danish researchers found.

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This study was designed to evaluate the relationship between ovarian reserve in a woman at a given age associated with her mother's age at menopause.

The study found a significant, positive association between age at maternal menopause and serum anti-Müllerian hormone levels and antral follicle count in daughters.

Women whose mothers experienced early menopause are themselves likely to have an accelerated decline in fertility, Danish researchers found.

Median serum levels of an important marker of ovarian reserve, anti-Müllerian hormone (AMH), declined by 8.6% (95% CI 6.4 to 10.8, P<0.001) yearly in women whose mothers entered menopause at or before age 45, according to Janne Gasseholm Bentzen, MD, PhD, and colleagues from the University of Copenhagen.

In contrast, women with maternal menopause at ages 46 to 54 had a decline in median AMH of 6.8% (95% CI 5 to 8.6, P<0.001) each year, while those with later maternal menopause had an annual decrease of only 4.2% (95% CI 2 to 6.4, P<0.001), the researchers reported in Human Reproduction.

During recent decades many women have delayed childbearing, with the possible result that they may then have difficulties in conceiving if their ovarian reserve has begun to be depleted and oocyte quality lost.

Many population-based studies have demonstrated a strong component of heritability for age at menopause, but whether this influence extends to fertility and ovarian viability has been unclear.

The mean number of antral follicles was 19, and median ovarian volume on ultrasound was 4.6 mL.

A linear relationship was seen for AMH and AFC, with a correlation coefficient of 0.82 (P<0.001).

Among women with early maternal menopause, AFC decreased annually by 5.8% (95% CI 4 to 7.5, P<0.001), the authors reported.

For those with normal-age maternal menopause, the decline was 4.7% (95% CI 3.3 to 6.1, P<0.001), while for late menopause the annual decrease was 3.2% (95% CI 1.4 to 4.9, P<0.001).

Both AMH and AFC were lower in women who used oral contraceptives, and AFC decreased by 11.1% (95% CI 0.1 to 21.1, P=0.04) in women whose mothers had smoked while pregnant.

No significant differences were seen for levels of estradiol or FSH, and ovarian volumes were similar across the groups.

The study confirmed that ovarian reserve in daughters may be influenced by maternal age at menopause, which may be a factor in the duration of their own reproductive lives, according to the researchers.

Being exposed to prenatal smoke also may contribute to earlier loss of fertility, they observed.

"The mechanisms underlying the decline of follicles with age remain far from being fully understood. The association between early menopausal age and the lower ovarian reserve measured through AMH and AFC could be either due to impaired oogenesis or due to prenatal loss during the fetal-life period," the researchers explained.

A strength of the study was its large population, but several limitations must be considered. The study was cross-sectional, so further longitudinal data will be needed.

In addition, participants were healthcare workers, who may be healthier than the general population, and there may have been recall bias for maternal age at menopause.

Environmental factors unmeasured in this study also may contribute to reproductive life and menopause, so "to provide an estimate of an individual woman's reproductive age, long-term follow-up studies are still required," the researchers concluded.

The study was funded by the Danish Agency for Science, Technology and Innovation, Copenhagen Graduate School of Health Science, and the Fertility Clinic at Copenhagen University Hospital.

The authors reported no conflicts of interest.

Reviewed by Zalman S. Agus, MD Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner

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